Abnormal brain inclusions characteristic of Alzheimer's disease (AD) are composed of paired helical filaments (')HF), a fibrillar form of tau ~HF-tau). Various purification methods with and without proteolysis give filaments with different properties. We are attempting to obtain clean specimens and measure both helical parameters and mass per unit length. Two different sucrose density gradient fractions of paired helical filaments (PHF) had different physical dimensions and masses. The size of the structural subunit can be estimated for both fractions. Recent studies involve the structure of ~aired helical) filaments grown in vitro with different isoforms of tau-protein. Mass/length measurements and radial mass profiles are being used to compare these filaments to in vivo PHFs and to look at the role of phosphorylation of tau. This is also in collaboration with Lester Binder at Northwestern.